[Delineating Concept for Defining the Country Practitioner - - An Objective Approach for Implementation in the Field of Health Services Research]. / Abgrenzungskonzeption zur Definition Landarzt.

In the context of the scientific discussions on health care research, a concrete and uniform definition of a country practitioner is still lacking. This would be essential, however, for the future design of the medical care structure in Germany. In particular, the ongoing discussions on the predicted shortage of physicians in rural and mostly economically undeveloped regions - a shortage that is already affecting parts of Germany - suggest the need for clarification of the concept of a country practitioner. Only on the basis of a uniform definition does it seem possible to develop and discuss effective solutions across regions and to be able to use them in a targeted manner. The multitude of existing approaches to solutions, which include, among others, telemedicine, health centres, community nurses, outpatient care services being undertaken by hospitals, and youth development, must be evaluated and adapted to actual needs. The article presents a newly developed multi-stage plan for the differentiation between rural and urban doctors, which enables the definition of "country practitioner" to be adapted according to the region. With the aid of the definition, a review and further development of the aforementioned approaches to solutions can take place. Moreover, by applying the concept of delineation, there is an opportunity to create completely new ideas and solutions in the context of health services research. The basis of the new approach to rural and urban medical delineation essentially consists of the following delineation steps: basic centre (Step I), rural settlement (Step II) and central geographic location (Step III). In the following, these 3 successive delineation steps are first separately and theoretically derived. Thereafter, the presented concept is applied to the region of Westphalia-Lippe. The developed model collectively offers a standardized approach that is feasible from a temporal and financial perspective. The primary aim of this paper is to contribute to the ongoing discussion on outpatient care research and, in particular, to the definition of the country practitioner. Using the model approach presented here, this definition also enables comparisons to be made between different regions of Germany.

[Methods of health economic evaluation for health services research]. / Methoden der gesundheitsökonomischen Evaluation in der Versorgungsforschung.

On August 30, 2010, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal [Gesundheitswesen 2010; 72: 739-748]. The present paper focuses on methodological issues of economic evaluation of health care technologies. It complements the Memorandum III "Methods for Health Services Research", part 2. First, general methodological principles of the economic evaluations of health care technologies are outlined. In order to adequately reflect costs and outcomes of health care interventions in the routine health care, data from different sources are required (e. g., comparative efficacy or effectiveness studies, registers, administrative data, etc.). Therefore, various data sources, which might be used for economic evaluations, are presented, and their strengths and limitations are stated. Finally, the need for methodological advancement with regard to data collection and analysis and issues pertaining to communication and dissemination of results of health economic evaluations are discussed.

[Transfer of the AGnES concept to the regular German health-care system: legal evaluation, reimbursement, qualification]. / Uberführung des AGnES-Konzeptes in die Regelversorgung: Juristische Bewertung, Vergütung, Qualifizierung.

INTRODUCTION: According to an amendment of German social security legislation, the AGnES concept of delegation of certain tasks of medical care, especially house calls, by general practitioners (GPs) to qualified practice employees (AGnES employees), will be transferred into the regular German health care system from January 2009 onward. The concept was developed to support GPs in regions with imminent gaps in primary care. METHODS: Patient data, the specifically delegated and all other activities carried out by the AGnES employees in the AGnES projects were digitally documented. Additionally, the participating GPs, AGnES employees and patients underwent a set of standardised interviews. A curriculum to qualify the AGnES employees and to define the requirements needed was developed. A legal assessment of all delegated activities was carried out, and an economical model to calculate the necessary allowance was calculated. RESULTS: In seven model projects in four federal states in Germany, 11,228 house calls were carried out involving 1,424, mostly multimorbid, patients (mean age: 78.6 years). A modular structured curriculum, considering the basic education and acquired competences, was developed. It allows for an individual qualification of the AGnES employees. The result of the legal assessment was the central relevance of the qualification of the practice employees according to the AGnES curriculum as the essential condition for carrying out the entire range of activities of the AGnES concept. The economic model revealed euro 21.58 for a house call by an AGnES employee. The underlying model referred to underserved regions. CONCLUSION: A successful transfer of the AGnES concept with a high standard of quality into regular health-care depends on several factors. Of particular importance is the specific qualification of the practice employees, which is a central legal condition for the delegation of medical tasks from GPs to AGnEs employees. A second determining factor is also an adequate reimbursement within the catalogus of the statutory health insurances.

[Population density, age distribution and urbanisation as factors influencing the frequency of home visits--an analysis for Mecklenburg-West Pomerania]. / Bevölkerungsdichte, Altersverteilung und Urbanität als Einflussfaktoren der Hausbesuchshäufigkeit - eine Analyse für Mecklenburg-Vorpommern.

BACKGROUND: This study examines and compares the frequency of home visits by general practitioners in regions with a lower population density and regions with a higher population density. The discussion centres on the hypothesis whether the number of home visits in rural and remote areas with a low population density is, in fact, higher than in urbanised areas with a higher population density. The average age of the population has been considered in both cases. METHODOLOGY: The communities of Mecklenburg West-Pomerania were aggregated into postal code regions. The analysis is based on these postal code regions. The average frequency of home visits per 100 inhabitants/km2 has been calculated via a bivariate, linear regression model with the population density and the average age for the postal code region as independent variables. The results are based on billing data of the year 2006 as provided by the Association of Statutory Health Insurance Physicians of Mecklenburg-Western Pomerania. In a second step a variable which clustered the postal codes of urbanised areas was added to a multivariate model. RESULTS: The hypothesis of a negative correlation between the frequency of home visits and the population density of the areas examined cannot be confirmed for Mecklenburg-Western Pomerania. Following the dichotomisation of the postal code regions into sparsely and densely populated areas, only the very sparsely populated postal code regions (less than 100 inhabitants/km2) show a tendency towards a higher frequency of home visits. Overall, the frequency of home visits in sparsely populated postal code regions is 28.9% higher than in the densely populated postal code regions (more than 100 inhabitants/km2), although the number of general practitioners is approximately the same in both groups. In part this association seems to be confirmed by a positive correlation between the average age in the individual postal code regions and the number of home visits carried out in the area. As calculated on the basis of the data at hand, only the very sparsely populated areas with a still gradually decreasing population show a tendency towards a higher frequency of home visits. CONCLUSION: According to the data of 2006, the number of home visits remains high in sparsely populated areas. It may increase in the near future as the number of general practitioners in these areas will gradually decrease while the number of immobile and older inhabitants will increase.

Dynamic expression patterns of the new protocadherin families CNRs and Pcdh-gamma during mouse odontogenesis: comparison with reelin expression.

Protocadherins are transmembrane glycoproteins belonging to the cadherin superfamily of molecules, which are involved in many biological processes such as cell adhesion, cytoskeletal organization and morphogenesis. Protocadherins generally exhibit only moderate adhesive activity and are highly expressed in the nervous system. Here, we report on the expression pattern of two novel families of protocadherins (CNRs and Pcdh-gamma) during rodent teeth development. Furthermore, we compare their expression with that of reelin, which is the potential ligand of CNRs. Throughout odontogenesis, CNRs, Pcdh-gamma and reelin show dynamic spatiotemporal expression patterns, which relate to both morphogenesis and cell differentiation events.

The characteristic cellular organization and CEACAM1 expression in the junctional epithelium of rats and mice are genetically programmed and not influenced by the bacterial microflora.

BACKGROUND: The epithelial cell adhesion molecule CEACAM1 exhibits an interesting dynamic expression during tooth development. It is first expressed in the reduced enamel epithelium, its expression then increases in the orally faced reduced epithelium and the overlying oral epithelium that then fuse to give rise to the junctional epithelium. The expression of CEACAM1 remains at high levels in the junctional epithelium, in contrast to the surrounding oral sulcular epithelium which shows much lower expression levels. We investigated if the high expression levels of CEACAM1 and the loosely organized cells characteristic of the junctional epithelium are genetically programmed or result from bacterial infiltration. METHODS: Oral tissues from germ-free rats and mice and animals with conventional bacterial flora were analyzed by transmission electron microscopy and immunohistochemical staining for CEACAM1. RESULTS: The junctional epithelium of both germ-free and conventional animals was identical with respect to both CEACAM1 expression and morphology. Also the presence of leukocytes was the same in both types of animals. CONCLUSIONS: The results indicate that the characteristic morphology and the high expression levels of CEACAM1 in the junctional epithelium are genetically programmed and not a result of bacterial infiltration. This suggests that CEACAM1 has an important role for the structural integrity of the junctional epithelium. This conclusion was supported by the observation that the junctional epithelium does not express any E-cadherin, which is another abundant epithelial cell adhesion molecule.

A double-blind, randomized, controlled study of amitriptyline, nortriptyline and placebo in patients with fibromyalgia. An analysis of outcome measures.

OBJECTIVE: To study the efficacy and tolerability of amitriptyline and nortriptyline in a Brazilian population with fibromyalgia and to evaluate the instruments used to measure the efficacy of the treatment. METHODS: A total of 118 fibromyalgia patients were randomly assigned to 3 groups: amitriptyline (AM, n = 40), nortriptyline (NOR, n =38) and placebo (PL, n = 40), and were blindly given 25 mg at bedtime of the assigned treatment for 8 weeks. Clinical evaluation before and at the end of the study included the number of tender points (NTP), FIQ score (FIQ), and global improvement as reported by the patients on a verbal scale (VSGI). RESULTS: The 3 groups were comparable at baseline for all the parameters studied. After 8 weeks, the 3 groups improved in all parameters: (36.5% AM, 26.7% NOR and 24% PL patients improved on FIQ; 13.9% AM, 19.5% NOR and 8.57% PL patients improved on NTP; 86.5% AM, 72.2% NOR and 57.6% PL patients improved on VSGI). Only the AM group differed from the PL group on VSGI. Side effects were noted among the groups, but none were serious (16 in the AM group, 31 in the NOR group, and 25 in the PL group). CONCLUSION: All three groups improved after treatment. Only the patient's subjective global assessment of improvement differed between the AM patients and the PL group (p < or = 0.03). In fibromyalgia, placebo groups are important in drug trials. Different measures of therapeutic effect are not better than the patient's self assessment.

Dynamic expression of E-cadherin in ameloblasts and cementoblasts in mice.

During embryonic development, E-cadherin mediates intercellular adhesion in a variety of epithelia in a spatio-temporal pattern. We have analyzed the distribution of this cell adhesion molecule in the mouse during odontogenesis, at both mRNA and protein levels, in the mandibular first molars and incisors. E-cadherin was strongly expressed at the bell stage by the cells of the dental organ, and by the pre-secretory ameloblasts and the cells of stratum intermedium at the early mineralization stage. At the onset of enamel secretion, E-cadherin disappeared from the apical pool of the ameloblasts and was later absent from the post-secretory ameloblasts. E-cadherin was also found in Hertwig's root sheath and later in the cells producing acellular cementum. These findings indicate that E-cadherin may be involved in the polarization of the ameloblasts and in the early stages of cementogenesis.

Binding of 2,6- and 2,7-dihydroxynaphthalene to wild-type and E-B13Q insulins: dynamic, equilibrium, and molecular modeling investigations.

The binding of phenolic ligands to the insulin hexamer occurs as a cooperative allosteric process. Investigations of the allosteric mechanism from this laboratory resulted in the postulation of a model consisting of a three-state conformational equilibrium and the derivation of a mathematical expression to describe the insulin system. The proposed mechanism involves allosteric transitions among two states of high symmetry, designated T3T3' (a low affinity state) and R3R3' (a high affinity state), and a third state of lower symmetry, designated T3oR3o (a state of mixed low and high affinities). To further characterize this mechanism, we present rapid kinetic fluorescence studies, equilibrium binding isotherms, and molecular modeling investigations for the Co(II)-substituted wild-type and E-B13Q mutant hexamers. These studies show that the measured on and off rates (kon and koff) for the binding of the allosteric ligands 2,6- and 2,7-dihydroxynaphthalene provide an independent measure of the dissociation constant for binding to the T3oR3o conformation (KRo). These constants are in agreement with the value obtained by computer fitting of the equilibrium binding isotherms to the quantitative allosteric mechanism. We analyze the structural differences between the T3oR3o and R6 phenolic binding sites and predict the structures of the T3oR3o-2,6-DHN and R6-2, 6-DHN complexes by 3-D molecular modeling. Assignment of H-bonding of the first hydroxyl group to CysA6 and CysA11 has been supported by stacking interactions analogous to phenol using 1H-NMR. H-bonding of the second hydroxyl group of 2,6-DHN to the GluB13 carboxylate side chains is predicted by molecular modeling and is supported by a reduction of affinity for Ca2+, which is postulated to bind to the GluB13 side chains.

Sensitivity and specificity of different diagnostic criteria for Behçet's disease according to the latent class approach.

In this study, we estimated the sensitivity and specificity of different criteria (International, Japanese, Mason & Barnes, O'Duffy, James and clinical judgement) for Behçet's Disease using the latent class approach. Thirty-two consecutive Behçet's Disease patients who were initially diagnosed according to clinical judgement, and 56 control patients with other rheumatic diseases, were recruited from the rheumatology out-patient clinic. The patients had their charts reviewed, were interviewed and clinically examined. Various models including different combinations of the six diagnostic criteria were tested. In the model that included all the information gathered, the International (sensitivity = 0.95, specificity = 1.00), Japanese (sensitivity = 1.00, specificity - 0.95) and Mason & Barnes criteria (sensitivity = 1.00, specificity = 0.94) were the most accurate. Clinician judgement also performed very well in identifying a Behçet's Disease case (sensitivity = 1.00, specificity = 0.85). The International, Japanese and Mason & Barnes criteria were the most accurate. The latent class method led to these conclusions without making any initial assumptions about the accuracy of any of the competing criteria (including clinical judgement).

The role of ambiental agents in Behçet's disease.

OBJECTIVE: To evaluate the potential role of environmental agents in the etiopathogenesis of Behçet's disease. METHODS: Twenty-eight Behçet's disease patients and 56 controls were recruited prospectively from the outpatient rheumatic disease clinic at the Escola Paulista de Medicina between July 1991 and July 1992. Behçet's disease was diagnosed using one of the accepted sets of criteria (Japanese Committee, International Committee, O'Duffy, Mason & Barnes, and James). The control patients, who had other rheumatic diseases, were matched on age and sex with the Behçet's disease patients. To investigate environmental factors, a standardized questionnaire was administered to each subject during an interview. Clinical and laboratory investigations were performed in each subject according to a predefined protocol. RESULTS: Analysis using the Chi-square test or Fisher's exact test (Cochran's restriction) disclosed significant associations between Behçet's disease and a history of herpes simplex virus type 1 infection or streptococcal infection. CONCLUSIONS: Despite the small sample size, our data strongly support a role of infectious agents in the etiopathogenesis of Behçet's disease. Further studies in larger patient populations are needed to confirm our results.

Immunohistochemical identification of myoepithelial, epithelial, and connective tissue cells in canine mammary tumors.

Fifty-eight formalin-fixed paraffin-embedded canine mammary tumors, 19 malignant and 39 benign, were used in this study. Tumors were obtained from dogs submitted for surgical resection of lesions at private veterinary practices in Brussels or from the surgery unit of the Faculty of Veterinary Medicine, University of Liège. Immunohistochemical evaluation was performed, using monoclonal antibodies directed against keratins 8-18 and 19, vimentin, desmin, and alpha-actin and polyclonal antibodies directed against high-molecular-weight keratins and S-100 protein. The main cell types, epithelial, myoepithelial, and connective, were identified, and myoepithelial cells represented the major component of most tumors, both benign and malignant. Myoepithelial cells had five patterns: resting and proliferative suprabasal cells, spindle and star-shaped interstitial cells, and cartilage. Reactivity to keratin 19, vimentin, alpha-actin, and S-100 protein suggested a progressive transformation from resting cells to cartilage. Epithelial cell reactivities were limited to keratins; only keratinized cells were positive for polyclonal keratins. Myofibroblasts were positive for both vimentin and alpha-actin, and connective tissue cells were positive for vimentin. Myoepithelial cells appeared to be the major component of carcinomas, justifying reevaluation and simplification of histomorphologic classifications, with a "pleomorphic carcinoma" group including all carcinomas except squamous, mucinous, and comedo carcinomas. Immunohistochemical evaluation, in addition to routine hematoxylin and eosin histopathologic evaluation is recommended for precise classification of canine mammary tumors.

Hypercoagulability in patients with peripheral vascular disease.

Twenty-seven patients with peripheral vascular disease had studies of thrombin generation, antithrombin III -alues, factor VIII values, platelet adhesitivity, and activated partial thromboplastin time. Of the studies performed, the thrombin generation index, antithrombin III values, and, to a lesser extent, activated partial thromboplastin time were reliable in confirming clinically suspected hypercoagulability. When patients were placed into groups with and without operative complications, it was noted that the group with operative complications had higher average values of thrombin generation index and lower average values of antithrombin III and activated partial thromboplastin time than did the group without operative complications. It is thought that these tests may be useful in selecting those patients with a high risk of thrombotic complications from vascular surgery and who may benefit from anticoagulant management while undergoing necessary vascular reconstructive procedures.